Left ventricle-only and right ventricular safety pacing in the context of multi-site left ventricular pacing

ABSTRACT

One way in which cardiac resynchronization therapy may be delivered is to only deliver paces to the left ventricle. If left ventricular pacing is inhibited during a cardiac cycle, it may be desirable to deliver a right ventricular safety pace to prevent asystole. Methods and devices for implementing right ventricular safety pacing in the context of multi-site left ventricular-only pacing are described.

CLAIM OF PRIORITY

This application claims the benefit of priority under 35 U.S.C. §119(e)of Stahmann et al., U.S. Provisional Patent Application Ser. No.61/424,962, entitled “LEFT VENTRICLE-ONLY AND RIGHT VENTRICULAR SAFETYPACING IN THE CONTEXT OF MULTI-SITE LEFT VENTRICULAR PACING”, filed onDec. 20, 2010, which is herein incorporated by reference in itsentirety.

FIELD OF THE INVENTION

This invention pertains to devices and methods for cardiac rhythmmanagement. In particular, the invention relates to a device and methodfor delivering cardiac resynchronization therapy.

BACKGROUND

Heart failure (HF) refers to a clinical syndrome in which an abnormalityof cardiac function causes a below normal cardiac output that can fallbelow a level adequate to meet the metabolic demand of peripheraltissues. Heart failure can be due to a variety of etiologies withischemic heart disease being the most common. Heart failure can betreated with a drug regimen designed to augment cardiac function or bypacing therapy. It has been shown that some heart failure patientssuffer from intraventricular and/or interventricular conduction defects(e.g., bundle branch blocks) such that their cardiac outputs can beincreased by improving the synchronization of ventricular contractionswith electrical stimulation. In order to treat these problems,implantable cardiac devices have been developed that provideappropriately timed electrical stimulation to one or more heart chambersin an attempt to improve the coordination of atrial and/or ventricularcontractions, termed cardiac resynchronization therapy (CRT).Ventricular resynchronization is useful in treating heart failurebecause, although not directly inotropic, resynchronization can resultin a more coordinated contraction of the ventricles with improvedpumping efficiency and increased cardiac output.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows the components of an exemplary device.

FIG. 2 is a block diagram of the electronic circuitry of an exemplarydevice.

FIGS. 3-6 illustrate the disclosed scheme for refractory periodmanagement for multi-site LV pacing.

FIGS. 7-10 illustrate implementation of a left ventricular protectiveperiod for multi-site LV pacing.

FIGS. 11-15 illustrate implementation of a biventricular-triggeredpacing mode for multi-site LV pacing.

DETAILED DESCRIPTION

Described herein are methods and devices that are specificallyapplicable to the delivery of cardiac resynchronization therapy usingmultiple left ventricular sites. Delivering such multi-site leftventricular pacing in an optimum manner requires modifications tocertain operational features that have been implemented in existingdevices for delivering cardiac resynchronization therapy as single-siteleft ventricular pacing. As described below, these features relate tothe management of refractory periods, the implementation of a leftventricular protective period, providing right ventricular safety pacingin a left ventricle-only pacing mode, and implementation of abiventricular-triggered pacing mode.

Hardware Description

Implantable pacing devices are typically placed subcutaneously orsubmuscularly in a patient's chest with leads threaded intravenouslyinto the heart to connect the device to electrodes disposed within aheart chamber that are used for sensing and/or pacing of the chamber. Aprogrammable electronic controller causes the pacing pulses to be outputin response to lapsed time intervals and/or sensed electrical activity(i.e., intrinsic heart beats not as a result of a pacing pulse). FIG. 1shows the components of an implantable pacing device 100 that includes ahermetically sealed housing 130 that is placed subcutaneously orsubmuscularly in a patient's chest. The housing 130 may be formed from aconductive metal, such as titanium, and may serve as an electrode fordelivering electrical stimulation or sensing in a unipolarconfiguration. A header 140, which may be formed of an insulatingmaterial, is mounted on the housing 130 for receiving leads 200 and 300which may be then electrically connected to pulse generation circuitryand/or sensing circuitry. Contained within the housing 130 is theelectronic circuitry 132 for providing the functionality to the deviceas described herein which may include a power supply, sensing circuitry,pulse generation circuitry, a programmable electronic controller forcontrolling the operation of the device, and a telemetry transceivercapable of communicating with an external programmer or a remotemonitoring device 190.

A block diagram of the circuitry 132 is illustrated in FIG. 2. A battery22 supplies power to the circuitry. The controller 10 controls theoverall operation of the device in accordance with programmedinstructions and/or circuit configurations. The controller may beimplemented as a microprocessor-based controller and include amicroprocessor and memory for data and program storage, implemented withdedicated hardware components such as ASICs (e.g., finite statemachines), or implemented as a combination thereof. As the term is usedherein, the programming of the controller refers to either code executedby a microprocessor or to specific configurations of hardware componentsfor performing particular functions. A telemetry transceiver 80 isinterfaced to the controller which enables the controller to communicatewith an external programmer and/or a remote monitoring unit. Sensingcircuitry 30 and pacing or pulse generation circuitry 20 are interfacedto the controller by which the controller interprets sensing signals andcontrols the delivery of pacing pulses in accordance with a pacing mode.The sensing circuitry 30 receives atrial and/or ventricular electrogramsignals from sensing electrodes and includes sensing amplifiers,analog-to-digital converters for digitizing sensing signal inputs fromthe sensing amplifiers, and registers that can be written to foradjusting the gain and threshold values of the sensing amplifiers. Thepulse generation circuitry 20 delivers pacing pulses to pacingelectrodes disposed in the heart and includes capacitive discharge pulsegenerators, registers for controlling the pulse generators, andregisters for adjusting pacing parameters such as pulse energy (e.g.,pulse amplitude and width). The pulse generation circuitry may alsoinclude a shocking pulse generator for delivering adefibrillation/cardioversion shock via a shock electrode upon detectionof a tachyarrhythmia.

A pacing channel is made up of a pulse generator connected to anelectrode, while a sensing channel is made up of a sense amplifierconnected to an electrode. Shown in the figure are electrodes 40 ₁through 40 _(N) where N is some integer. The electrodes may be on thesame or different leads and are electrically connected to a MOS switchmatrix 70. The switch matrix 70 is controlled by the controller and isused to switch selected electrodes to the input of a sense amplifier orto the output of a pulse generator in order to configure a sensing orpacing channel, respectively. The device may be equipped with any numberof pulse generators, amplifiers, and electrodes that may be combinedarbitrarily to form sensing or pacing channels. The switch matrix 70allows selected ones of the available implanted electrodes to beincorporated into sensing and/or pacing channels in either unipolar orbipolar configurations that may be either atrial or ventricular channelsdepending upon the location of the electrode.

The device is also equipped with a minute ventilation sensor 25 formeasuring the patient's minute ventilation and an activity level sensor26. The activity level sensor may be any type of motion detector such asan accelerometer inside the pacemaker case that responds to vibrationsor accelerations and, after appropriate filtering, produces electricalsignals proportional to the patient's level of physical activity. Theminute ventilation sensor includes a pair of current source electrodesand a pair of voltage sense electrodes for measuring transthoracicimpedance. In rate-adaptive pacing, the pacemaker uses the sensed minuteventilation and/or the accelerometer signal to adjust the rate at whichthe pacemaker paces the heart in the absence of a faster intrinsicrhythm.

Pacing Modes for Cardiac Resynchronization Therapy

The controller is capable of operating the device in a number ofprogrammed modes where a programmed mode defines the sensing and pacingchannels used by the device and how the pacing pulses are output inresponse to sensed events and expiration of time intervals. Cardiacresynchronization therapy is most conveniently delivered in conjunctionwith a bradycardia pacing mode. Bradycardia pacing modes refer to pacingalgorithms used to pace the atria and/or ventricles in a manner thatenforces a certain minimum heart rate. Because of the risk of inducingan arrhythmia with asynchronous pacing, most pacemakers for treatingbradycardia are programmed to operate synchronously in a so-calleddemand mode where sensed cardiac events occurring within a definedinterval either trigger or inhibit a pacing pulse. Inhibited demandpacing modes utilize escape intervals to control pacing in accordancewith sensed intrinsic activity such that a pacing pulse is delivered toa heart chamber during a cardiac cycle only after expiration of adefined escape interval during which no intrinsic beat by the chamber isdetected. In conventional dual-chamber pacing (i.e., pacing pulsesdelivered to the right atrium and the right ventricle), a ventricularescape interval for pacing the ventricles can be defined betweenventricular events, referred to as the cardiac cycle interval (CCI),where the CCI is restarted with a ventricular sense or pace. The inverseof the CCI is the lower rate limit or LRL, which is the lowest rate atwhich the pacemaker will allow the ventricles to beat. In atrialtracking and AV sequential pacing modes, another ventricular escapeinterval is defined between atrial and ventricular events, referred toas the atrio-ventricular pacing delay interval or AVD, where aventricular pacing pulse is delivered upon expiration of theatrio-ventricular pacing delay interval if no ventricular sense occursbefore. In an atrial tracking mode or AV sequential mode, theatria-ventricular pacing delay interval is triggered by an atrial senseor pace, respectively, and stopped by a ventricular sense or pace.Atrial tracking and AV sequential pacing are commonly combined so thatan AVD starts with either an atrial pace or sense. An atrial escapeinterval can also be defined for pacing the atria, either alone or inaddition to pacing the ventricles, as an escape interval started by aventricular sense or pace and stopped by an atrial sense or pace.

As described above, cardiac resynchronization therapy is pacingstimulation applied to one or more heart chambers in a manner thatcompensates for conduction delays. Cardiac resynchronization therapy ismost commonly applied in the treatment of patients with heart failuredue to left ventricular dysfunction which is either caused by orcontributed to by left ventricular conduction abnormalities. In suchpatients, the left ventricle or parts of the left ventricle contractlater than normal during systole which thereby impairs pumpingefficiency. This can occur during intrinsic beats and during paced beatswhen only the right ventricle is paced. In order to resynchronizeventricular contractions in such patients, pacing therapy is appliedsuch that a portion of the left ventricle is pre-excited by a pacerelative to when it would become depolarized during an intrinsic orright ventricle-only paced beat. Optimal pre-excitation of the leftventricle in a particular patient may be obtained with biventricularpacing, where pacing pulses are delivered to the right and leftventricles separated by a specified negative or positive offsetinterval, or with left ventricle-only pacing.

Existing devices have been configured to deliver biventricular or leftventricle-only pacing using a bradycardia mode based on right heartevents. In these modes, an escape interval for delivering paces to theventricle is restarted (or stopped in the case of the AVD) by a rightventricular pace or sense. A right ventricular sense thus inhibitsventricular pacing, and expiration of the escape interval results in aright ventricular pace, with left ventricular pacing scheduled to occurbefore or after the expiration. In the case of left-ventricle-onlypacing, expiration of the escape interval is marked by a rightventricular pseudo-pace acting as a fiducial point.

CRT has been conventionally delivered as left ventricle-only orbiventricular pacing where the left ventricle is paced at a singlepacing site, referred to herein as single-site LV pacing. Certainpatients may benefit, however, from CRT that delivers paces to multipleleft ventricular sites, referred to herein as multi-site LV pacing.Although it is straightforward to transfer certain device behaviors fromsingle-site LV pacing to multi-site LV pacing, others requiremodification for optimum performance. As discussed below, these devicebehaviors relate to the management of sensing channel refractoryperiods, operation of the left ventricular protective period, leftventricle-only pacing in conjunction with right ventricular safetypacing, and switching between LV-only and biventricular triggeredpacing.

Refractory Periods for Multi-Site Left Ventricular Pacing

A refractory period for a pacemaker sensing channel refers to a periodof time during which the sensing channel is either blind to incomingelectrical signals, termed a blanking interval, and/or during which thedevice is configured to ignore such signals for purposes of sense eventdetection. It is conventional to blank sensing amplifiers for aninterval of time following delivery of a pacing pulse to prevent theirsaturation. Sensing channels are also rendered refractory after certainpace and sense events in order avoid sensing electrode afterpotentialsand preventing cross-talk between the different sensing channels.Refractory periods also often include a retriggerable noise window,where the noise interval usually constitutes the last part of therefractory period. Sensed events occurring within the noise intervalwill restart the noise interval, thus increasing the length of therefractory period.

Existing devices configured to deliver single-site LV pacing may utilizea right atrial sensing channel, a right ventricular sensing channel, anda left ventricular sensing channel. Refractory periods for the sensingchannels in these devices are managed as follows: 1) a sense occurringin a particular sensing channel initiates a refractory period ofspecified duration for that particular sensing channel, 2) a rightatrial refractory period of specified duration is initiated by a rightatrial pace, 3) a right atrial refractory period of specified durationis initiated by a left ventricular or right ventricular pace, 4) a leftventricular refractory period of specified duration is initiated by aright or left ventricular pace, and 5) a right ventricular refractoryperiod of specified duration is initiated by a right or left ventricularpace. Although this scheme is adequate for single-site LV pacing,modifications are necessary for optimal performance in multi-site LVpacing.

FIGS. 3-6 illustrate the disclosed scheme for refractory periodmanagement in a multi-site LV pacing situation. Each of the figuresshows time lines for the right atrial (A) sensing channel, the rightventricular (RV) sensing channel, and the left ventricular (LV) sensingchannel for various programmed settings and cardiac cycle types. Theshaded blocks along each time line indicate that the sensing channel isrefractory, and the dashed-line block along the LV time line indicates aleft ventricular protective period (LVPP) as discussed below. As shownin FIGS. 3-6, the behavior for post-sense refractory periods that areinitiated by a right atrial sense AS, a right ventricular sense RVS, ora left ventricular sense LVS is that a sense occurring in a particularsensing channel initiates a refractory period of specified duration forthat particular sensing channel.

FIG. 3 illustrates the situation for dual-site LV pacing where the LV ispaced before the RV, while FIG. 4 illustrates the situation fordual-site LV pacing where the RV is paced first. FIG. 5 illustratesdual-site LV-only pacing where the first left ventricular pace LVP1 to afirst LV site is coincident with the right ventricular pseudo-pace [RVP]and the second left ventricular pace LVP2 to a second LV site isdelivered afterwards. FIG. 6 illustrates dual-site LV-only pacing wherethe first left ventricular pace LVP1 occurs before the second leftventricular pace LVP2 coincident with the right ventricular pseudo-pace[RVP]. Note that, in FIG. 3, when RV and LV refractory periods areinitiated by a left ventricular pace LVP1, a subsequent left ventricularpace LVP2 and right ventricular pace RVP do not affect those ventricularrefractory periods In FIG. 4, when RV and LV refractory periods areinitiated by a right ventricular pace RVP, these ventricular refractoryperiods are unaffected by a subsequent left ventricular pace LVP1 andleft ventricular pace LVP2. In both FIGS. 5 and 6, the RV and LVrefractory periods initiated by LVP1 are unaffected by LVP2 or the rightventricular pseudo-pace [RVP]. Also, in each situation, the LVP1 andLVP2 paces each triggers an RA refractory period that may use the samesettings. Note also that, in all cases, the LVP2 pace does not extendthe LVPP initiated by the LVP1 pace.

FIGS. 3-6 show that an RA refractory period is started by a right atrialpace AP. Also, the LVP1 pace starts an RA refractory period, and thesubsequent LVP2 pace starts a new RA refractory period. The two RArefractory periods initiated by left ventricular paces preferably sharethe same settings. Also, if the LVP2 pace falls within the RA refractoryperiod initiated by the LVP1 pace, the RA refractory period initiated byLVP1 terminates. The rationale for this scheme is to restart the RArefractory period after LVP2 for all the same reasons as after LVP1,including restarting the AGC (automatic gain control) and the absoluteand retriggerable components of the refractory period. In anotherembodiment, the LVP2 pace, rather than starting a new RA refractoryperiod, extends the RA refractory period initiated by LVP1 by theLVP1-to-LVP2 interval. Note that this is not the same as starting a newrefractory period since the retriggerable components and AGC would bedifferent.

FIGS. 3-6 also show that both the RV and LV post-pace refractory periodsstart on the first ventricular pace in the pacing sequence that createsa ventricular depolarization.

The post-pace refractory periods for RV and LV are the preferably thesame for LVP1 and LVP2. Note that, if one or more LV paces is inhibited(e.g., due to the LVPP), then the RV and LV post-pace refractory periodsstart for all ventricular sensing channels on the first remainingventricular pace in the pacing sequence that creates a ventriculardepolarization. The refractory behavior depicted in FIGS. 3-6 can alsobe extended to more than one LV sensing channel and more than two LVpacing sites.Left Ventricular Protection Period for Multi-Site Left VentricularPacing

In a pacing mode where the left ventricle is paced upon expiration of anescape interval that is reset by a right ventricular sense, there is therisk that the left ventricular pace may be delivered in the so-calledvulnerable period that occurs after a depolarization and trigger anarrhythmia. To reduce this risk, existing devices that deliversingle-site LV pacing based on right heart events have implemented aleft ventricular protective period (LVPP) that is initiated by a leftventricular sense or pace and during which further left ventricularpacing is inhibited. FIG. 7 depicts the behavior of the LVPP algorithmin existing devices. All LV paces are inhibited during LVPP other thanthe LV pace that triggers LVPP. Either a non-refractory LV sense or anLV pace initiates LVPP. A non-refractory LV sense during LVPP restartsLVPP and therefore extends the LV pace inhibition period.

Delivery of a multiple LV pacing pulses during a single cardiac cyclerequires that the LVPP behavior employed in those existing devices bemodified. Without modification, the LV pacing pulses after the firstpulse would be inhibited by LVPP, and some additional pacing hazards maybe unmitigated. Several options exist for LVPP behavioral modification;any of which will prevent inhibition of LV pacing pulses after the firstLV pacing pulse while mitigating the LV pacing hazard associated with LVpacing. As described below, there are advantages and disadvantages tothe various options.

In one option, illustrated for dual-site LV pacing, the existing singleLVPP interval is replaced by two LVPP intervals. These two intervalswould act independently, the first inhibiting pacing of LV pacing site 1and the second inhibiting pacing of LV pacing site 2. The behavior ofthe each LVPP intervals is similar to the existing single LVPP interval.Note that the two LVPP intervals are protecting pacing sites and thatthese sites could be paced in different sequences in different cardiaccycles. FIG. 8 illustrates this embodiment. As shown, the first LV paceLVP1 is delivered to LV pacing site 1 and initiates left ventricularprotective period LVPP1. The second LV pace LVP2 is delivered to LVpacing site 2 and initiates left ventricular protective period LVPP2.The RV pacing pulse may be delivered before LVP1, after LVP2 or inbetween LVP1 and LVP2. LV paces at the first LV site are inhibitedduring LVPP1, and LV paces at the second LV site are inhibited duringLVPP2. Also as shown in FIG. 8, either a non-refractory LVS or LVP1initiates LVPP1, and all LV1 paces are inhibited during LVPP1 other thanthe LVP1 pace that triggered LVPP1. Similarly, either a non-refractoryLVS or LVP2 initiates LVPP2, and all LVP2 paces are inhibited duringLVPP2 other than the LVP2 pace that triggered LVPP2.

In the particular embodiment illustrated by FIG. 8, two left ventricularsensing channels are used that generate separate sense signals LVS1 andLVS2 from the LVP1 and LVP2 pacing sites, respectively. As depicted,LVS1 and LVS2 may trigger LVPP1 and LVPP2, respectively. Alternatively,the same LVS may be used as a trigger for both LVPP intervals. Thisoption could be used if only a single LV sensing channel is available.Also, a non-refractory LVS retriggers one or both (depending on if oneor two LV senses are used) LVPP intervals. This option can be extendedto an arbitrary number of LV pacing sites. For example, four LVPPintervals may be used if four LV pacing sites are paced within a singlecardiac cycle. An advantage of this option is that each LV site isprotected by its own protection period. Another advantage of usingmultiple LV sense inputs is that it most clearly protects individual LVpacing sites. A disadvantage of multiple LVPP intervals is that thesystem must manage multiple protection periods within the device and onthe user interfaces. A disadvantage of using multiple LV sensingchannels is that the system must include additional sensing hardware andmanage multiple sensing vectors.

In a second option, a single LVPP interval is used. The LVPP behavior issimilar to the existing LVPP behavior except that one LV pacing pulseper LV pacing site is delivered. Specifically, for LVPP intervalstriggered by an LV pace, the first LV pace, but only the first pace, perLV pacing site during LVPP is delivered. All other LV paces areinhibited. For LVPP intervals triggered by an LV sense, all LV pacesduring the LVPP interval are inhibited. The LVPP interval is retriggeredby a non-refractory LV sense, but not by LV paces during the LVPPinterval (other than the initiating LV pace for LVPP intervals triggeredby an LV pace). FIG. 9 illustrates this embodiment. As depicted, eithera non-refractory LVS or an LVP to any site initiates LVPP. The LV pacethat initiates the LVPP is not inhibited. A non-refractory LV senseduring LVPP restarts the LVPP and therefore extends the LV paceinhibition period. The LV pace LVP2 at the second site is not inhibitedby the LVPP, and LV paces during the LVPP do not retrigger the LVPP.When using a single LVPP, the LVP1 and LVP2 paces should be closelyspaced (e.g. within 100 ms). Given this condition, the rationale for notrestarting LVPP on the LVP2 pace is that a subsequent LVP1 will notoccur soon enough to fall within an LV vulnerable period of the LVP2pacing site. Also, in this embodiment, LVP2 is inhibited during an LVPPinitiated by LVP1 if a non-refractory LV sense occurs between thedelivered LVP1 and the inhibited LVP2. As shown in FIG. 9, a single LVsense LVS may trigger and retrigger LVPP. This option could be used ifonly a single LV sensing channel is available. Alternatively, LV sensesfrom multiple LV sensing channels may be used as a trigger and retriggerthe LVPP interval. The advantage of the single LVPP interval issimplicity; only one interval needs to be managed within the pulsegenerator and on the user interfaces. This option still providesadequate protection if the LV pace pulse spacing condition noted aboveis met. The disadvantage of the single LVPP interval is that some levelof LV site pacing protection may be lost as compared to the option usingmultiple protection periods.

In a third option, a single LVPP interval is also used, but LV pacesafter the first LV pace retrigger the LVPP interval. This embodiment isdepicted in FIG. 10. For LVPP intervals triggered by an LV pace, onlythe first LV pace per LV pacing site during LVPP is delivered, and allother LV paces are inhibited. For LVPP intervals triggered by an LVsense, all LV paces during the LVPP are inhibited. Either anon-refractory LVS or an LVP to any site initiates the LVPP. Anon-refractory LV sense during LVPP restarts LVPP and therefore extendsthe LV pace inhibition period. The LVP2 pace is not inhibited by theLVPP initiated by LVP1. The second LVP2 restarts the LVPP and thereforeextends the LV pace inhibition period. Also as shown in FIG. 10, LVsenses LVS from a single LV sensing channel trigger and retrigger theLVPP. This option could be used if only a single LV sensing channel isavailable. Alternatively, multiple LV sense inputs (e.g. LVS1 and LVS2)from multiple LV sensing channels may trigger and retrigger the LVPPinterval. In one embodiment the LVPP extension due to LVP2 is the sameas the initial LVPP interval, while in other embodiments it is eithershorter or longer than the initial LVPP interval. This option may berequired if the LV paces are spaced such that an LVP1 pace may fallwithin an LV vulnerable period of the LVP2 pacing site.

The LVPP can interfere with high rate LV pacing. To avoid or minimizethis problem, the LVPP can be shortened as heart rate increases. Ifimplemented appropriately, this does not place the patient at risk forpacing during the vulnerable time since the QT interval normallyshortens (i.e., the vulnerable time moves toward the LV event) withincreasing heart rate. This concept (sometimes referred to as LVPPsqueeze) is implemented in existing devices and can be extended tooperate with any of LVPP schemes for multi-site LV pacing describedabove.

Another type of protection for the left ventricle implemented inexisting single-site LV pacing devices is the ensuring a minimumseparation between adjacent pacing LV paces during consecutive cardiaccycles to prevent LV pacing into a vulnerable time. This parameter isthe minimum LV pacing interval, designated LVPI. Some physicians maywish to disable LVPP due to, for example, over sensing in the LV causinginappropriate inhibition of LV pacing therapy. If LVPP is disabled apacing hazard, somewhat hidden from the physician, still needs to bemitigated. The specific hazard arises during, for example, a transitioncycle from positive LV offset pacing to negative offset LV pacing wherethe LV pace is delivered after and before, respectively, the rightventricular pace (or pseudo-pace). Because the next LV pace in thetransition cycle occurs sooner than in previous cycles, there is a riskit will occur during the vulnerable period.

Devices capable of multi-site LV pacing may use the same rules forimplementing the LVPI as used for implementing the LVPP. Possibleexceptions could be that LVPI is triggered only after an LV pace andthat LVPI cannot be disabled by the user. Existing systems invoke LVPIon transition cycles where the LV offset changes, and this can also beimplemented in multi-site LV systems. However in multi-site LV systems,LVPI may also need to be invoked on transition cycles where: 1) the LVpace to LV pace (e.g. LVP1 to LVP2) interval(s) change, or 2) anadditional LV pace is added.

Multi-Site Left Ventricle-Only Pacing and Right Ventricular SafetyPacing

As described above, the LVPP provides protection for the left ventriclewhen triggered by an LVS. In LV-only pacing, however, if the LVS is dueto oversensing, asystole may result. To remedy this, existing devicesmay employ a right ventricular safety pace that is delivered in place ofthe right ventricular pseudo-pace when an LVS but no RVS occurs. Thebasic timing behavior of LV-only pacing in DDD mode in existing devicesis that an LV pace is issued at the end of the AV delay unless an RVsense restarts the cardiac cycle interval CCI, LVPP or LVPI inhibits theLV pace, or an LV pace violates the specified minimum CCI interval. Ifthe LV pace is inhibited by LVPP or LVPI, then an RV safety pace isissued instead of the LV pace. If the LV pace would violate the minimumcardiac cycle interval, then the LV pace is delayed to the point wherethe minimum cardiac cycle interval would not be violated. This scheme isappropriate for single-site LV-only pacing but is inadequate formulti-site LV-only pacing.

In a presently disclosed scheme for multi-site LV-only pacing with rightventricular safety pacing, the LV paces are issued at the end of the AVdelay (in e.g., DDD mode) or CCI (in e.g., VVI mode) unless: an RV senserestarts the cardiac cycle interval, LVPP or LVPI inhibits some or allof the LV paces, or one or more of the LV paces violates the minimumCCI. All LV paces that would violate the minimum CCI will be delayed orinhibited All cardiac cycles are defined using only RV events such thatan RV pseudo-pace acts as the fiducial for the cardiac cycle when no RVsense occurs. The RV pseudo-pace may, but does not need to, occurcoincident with one of the LV paces for cycles where the onlyventricular paces are delivered to the left ventricle. An RV safety paceis delivered if all LV paces are inhibited due to LVPP or LVPI and maybe issued if some LV paces are inhibited clue to LVPP or LVPI.

With regard to the delivery of LV paces, options for implementing themulti-site LV-only pacing scheme as described above include thefollowing (which may be used alone or in combination):

-   -   1. Inhibit all LV paces that occur within LVPP or LVPI, deliver        any LV paces scheduled for delivery after expiration of LVPP or        LVPI at their scheduled times and        -   a. Do not pace the inhibited LV sites for current cardiac            cycle.        -   b. Pace inhibited LV sites immediately after expiration of            LVPP or LVPI.    -   2. If all LV paces before or coincident with the end of the AV        delay (in e.g. DDD mode) or CCI (in e.g. VVI mode) are inhibited        (due to LVPP or LVPI) but there is at least one LV pace        scheduled for delivery after expiration of LVPP or LVPI then        -   a. Deliver all LV paces that fall outside LVPP and LVPI at            their scheduled times.        -   b. Deliver all LV paces that fall outside LVPP and LVPI            immediately after expiration of LVPP or LVPI.        -   c. Deliver LV paces scheduled inside LVPP and LVPI,            immediately after expiration of LVPP or LVPI and all            remaining LV paces at their scheduled times.        -   d. Deliver all LV paces, including those scheduled inside            LVPP and LVPI, immediately after expiration of LVPP or LVPI,        -   e. Deliver all LV paces, including those fall inside LVPP            and LVPI, immediately after expiration of LVPP or LVPI.        -   f. Inhibit all remaining LV paces even though they fall            outside LVPP or LVPI.    -   3. If all LV paces before or coincident with the end of the AV        delay (in e.g. DDD mode) or CCI (in e.g. VVI mode) are not        inhibited but LV paces after the end of the AV delay or CCI are        inhibited then do not issue an RV safety pace.

In the pacing schemes described herein, all cardiac cycles are definedusing only RV events. In one embodiment, an RV pseudo-pace acting as thefiducial for the cardiac cycle occur coincident with one of the LV pacesfor cycles where the only ventricular paces are delivered to the leftventricle. Additional behavior options (not mutually exclusive) for thisembodiment include:

1) Align the RV pseudo pace with the end of the AV delay (e.g., in DDDmode) or CCI (e.g., in VVI mode) and one of the LV paces and

-   -   a. Allow additional LV paces only before or coincident with the        RV pseudo pace.    -   b. Allow additional LV paces only after or coincident with the        RV pseudo pace.    -   c. Allow additional LV paces before, after or coincident with        the RV pseudo pace.

2) Align the RV pseudo-pace with the end of the AV delay (e.g., in DDDmode) or CCI (e.g., in VVI mode) but not one of the LV paces.

Options 1a and 1b above may simplify the user interface and possibly theuser's understanding of the system's behavior.

As noted above, in the presently disclosed scheme, an RV safety pace isdelivered if all LV paces are inhibited due to LVPP or LVPI and may beissued if some LV paces are inhibited due to LVPP or LVPI. It shouldalso be noted LV pacing can be inhibited by noise, and this rule mayapply to noise inhibited LV paces as well as LVPP or LVPI inhibitedpaces.) A complicating factor in multi-site LV pacing is that one ormore of the leading LV paces may be inhibited but one or more of thelagging LV paces may not be inhibited. (For example, the LVPP may expireduring the LV pacing sequence). Another complicating factor is that theLV pace coincident with the RV pseudo-pace may be inhibited while laterscheduled LV paces are not inhibited. Therefore to ensure that the AVdelay and CCI rules are met, RV safety pacing may be required even ifone or LV paces fall outside of the LVPP or LVPI intervals. Options forimplementing the multi-site LV-only pacing scheme as just describedinclude the following (which may be used alone or in combination):

1) If all the LV paces are inhibited (due to LVPP or LVPI) then deliveran RV

safety pace coincident with the RV pseudo-pace.

2) If one or more LV paces are inhibited (due to LVPP or LVPI) but thereis at least one LV pace scheduled for delivery after expiration of LVPPor LVPI, then deliver all LV paces that fall outside LVPP and LVPI attheir scheduled times and

-   -   a. Do not deliver an RV safety pace regardless of which LV paces        were inhibited.    -   b. If all LV paces before and coincident with the RV pseudo-pace        are inhibited then        -   i. Deliver an RV safety pace coincident with the RV            pseudo-pace and inhibit all remaining LV paces even though            they fall outside LVPP or LVPI.        -   ii. Deliver the RV safety pace coincident with the RV            pseudo-pace and deliver all remaining LV paces that fall            outside LVPP and LVPI at their scheduled times.        -   iii. Deliver the RV safety pace coincident with the RV            pseudo-pace and deliver all remaining LV paces immediately            after expiration of LVPP or LVPI.

3) If only LV paces after the RV pseudo-pace are inhibited, then do notissue an RV safety pace. (Note: This cannot happen if LV pace refractorytime, triggered by the first LV pace, is longer than the duration of theLV pacing sequence)

Biventricular-Triggered Mode for Multi-Site Left Ventricular Pacing

In order to optimally resynchronize the ventricles during normaldelivery of CRT, the ventricles are paced before intrinsic activationoccurs at either of the ventricular pacing sites. However, in some casesintrinsic activation occurs before the scheduled

time for pacing pulse delivery. These “escape beats” can occur, forexample, during atrial arrhythmias due to the irregular atrial rate orat elevated heart rates due to decreased PR intervals. To at leastpartially resynchronize the ventricles during these escape beats,existing devices have implemented a biventricular-triggered pacing modethat is switched to when conditions such as mentioned above occur. Inthis mode, paces are delivered to both the right and left ventricularpacing sites if intrinsic activity is detected at the right ventricularpacing site (i.e. an RV sense occurs). The premise of the algorithm isthat, although depolarization has occurred at the right ventricularsite, the left ventricular site can still be at least somewhatsynchronized by pacing it immediately after the RV sense. Since the RVsense may actually be caused by detection of an LV far field event (inwhich case it is the RV that needs to be paced), both the RV and LV arepaced upon occurrence of an RV sense. Biventricular-triggered pacing, asimplemented in existing devices, does not accommodate multi-site LVpacing. This is depicted in FIG. 11. During normal cycles the RV and LVare paced before intrinsic activation occurs at either pacing site.During a biventricular-triggered or BT cycle, both right and leftventricular pacing pulses are delivered immediately after the RV sense.

Different embodiments for implementing a biventricular-triggered pacingmode in a multi-site LV pacing situation are illustrated by FIGS. 12-15.For all the embodiments, during normal cycles the RV and multiple LVsites are paced before intrinsic activation occurs at any pacing site. Afirst embodiment is illustrated by FIG. 12 where, during a BT cycle, theRV and only one of the multiple LV sites are paced immediately after anRV sense. The single LV site is selected from the multiple LV sites todeliver the best resynchronization therapy. The LV site paced during BTtherapy may be selected from the LV sites enabled for pace delivery onnormal cycle or selected from an LV site that is not enabled for pacedelivery in a normal cycle. A second embodiment is illustrated by FIG.13 where, during a BT cycle, the RV and two or more of the multiple LVsites are paced immediately after an RV sense. The LV sites paced duringBT therapy may be selected from the LV sites enabled for pace deliveryon normal cycle, may be selected from LV sites that are not enabled forpace delivery in a normal cycle, or may selected from a combination ofLV sites enabled and of LV sites not enabled for pace delivery in anormal cycle. A third embodiment is illustrated by FIG. 14 where, duringa BT cycle, the RV and one or more of the multiple LV sites are pacedimmediately after an RV sense. In this embodiment, at least one of theLV sites is paced after the first LV pace(s), and the RV pace occurssimultaneous with or before any LV pace. (It should be appreciated that“simultaneous” in this context means approximately or physiologicallysimultaneous. Multiple paces delivered at exactly the same time mayresult in undesirable electrical current paths that can alter pacingthresholds and electrode charge balance. To avoid this effect, paces canbe delivered with a small offset (5 ins) and still providephysiologically simultaneous stimulation.) The LV paces sites and/orLV-to-LV interval(s) in the BT cycle may be the same or different asthose used in the normal cycle. A fourth embodiment is illustrated byFIG. 15 where, during a BT cycle, the RV and one or more of the multipleLV sites are paced immediately after an RV sense. In this embodiment, atleast one of the LV sites is paced after the first LV pace(s), and theRV pace occurs after at least one of the LV paces.

Exemplary Embodiments

In the exemplary embodiments described below, a cardiac pacing deviceincludes pulse generation circuitry for generating pacing pulses,sensing circuitry for sensing cardiac electrical activity, a controllerfor detecting cardiac events that define pacing timing intervals and forcontrolling the delivery of pacing pulses in accordance with aprogrammed mode, and a switch matrix operable by the controller forconnecting the pulse generation circuitry and sensing circuitry toselected electrodes in order to form selected sensing and pacingchannels. The controller is then programmed to form the appropriatepacing and sensing channels and deliver multi-site LV pacing using thedifferent schemes described herein.

In an exemplary embodiment for implementing refractory periods, where arefractory period is either when a sensing channel is disabled or whensensed activity is ignored for purposes of cardiac event detection, thecontroller is programmed to sense cardiac activity through a rightventricular sensing channel, schedule delivery of paces through leftventricular pacing channels to at least two left ventricular sitesdesignated LV1 and LV2 during a cardiac cycle interval that is reset bya right ventricular sense, and initiate a post-pace refractory periodfor the right ventricular sensing channel when the first ventricularpace is delivered during a cardiac cycle. The controller may further beprogrammed to: 1) sense cardiac activity through a left ventricularsensing channel and initiate a post-pace refractory period for the leftventricular sensing channel when the first ventricular pace is deliveredduring a cardiac cycle; 2) initiate a post-sense refractory period forany sensing channel when a sense is detected in that sensing channel; 3)sense atrial activity through an atrial sensing channel and initiate apost-pace refractory period for the atrial sensing channel for eachventricular pace delivered during a cardiac cycle; 4) initiate thepost-pace refractory periods upon delivering the left ventricular pacesto sites LV1 and LV2 use the same programmed settings; 5) deliver a paceto the right ventricle through a right ventricular pacing channel duringa cardiac cycle interval and subsequently deliver left ventricular pacesto sites LV1 and LV2 during to the cardiac cycle interval unlessinhibited by a right ventricular sense, reset the cardiac cycle intervalupon either a right ventricular sense or a right ventricular pace, afterinitiation of post-pace refractory periods for the right and leftventricular sensing channels when the right ventricular pace isdelivered, leave the post-pace refractory periods unaffected by thesubsequent paces to LV1 and LV2; 6) after delivery of delivery of leftventricular paces to sites LV1 and LV2, deliver a pace to the rightventricle through a right ventricular pacing channel during a cardiaccycle interval unless inhibited by a right ventricular sense, reset thecardiac cycle interval upon either a right ventricular sense or a rightventricular pace, after initiation of post-pace refractory periods forthe right and left ventricular sensing channels when a first ventricularpace is delivered to site LV1, leave the post-pace refractory periodsunaffected by the subsequent pace to site LV2 and the right ventricularpace; 7) deliver a left ventricular pace to site LV1 coincident with aright ventricular pseudo-pace and subsequently deliver a leftventricular pace to site LV2 during a cardiac cycle interval unlessinhibited by a right ventricular sense, reset the cardiac cycle intervalupon either a right ventricular sense or a right ventricularpseudo-pace, after initiation of post-pace refractory periods for theright and left ventricular sensing channels when a first ventricularpace is delivered to site LV1, leave the post-pace refractory periodsunaffected by the subsequent pace to site LV2; 8) deliver a leftventricular pace to site LV1 and subsequently deliver a left ventricularpace to site LV2 coincident with a right ventricular pseudo-pace duringa cardiac cycle interval unless inhibited by a right ventricular sense,reset the cardiac cycle interval upon either a right ventricular senseor a right ventricular pseudo-pace, after initiation of post-pacerefractory periods for the right and left ventricular sensing channelswhen the pace is delivered to site LV1, leave the post-pace refractoryperiods unaffected by the subsequent pace to site LV2; and/or 9) delivera left ventricular pace to site LV1 and subsequently deliver a leftventricular pace to site LV2 during a cardiac cycle, initiate a leftventricular protective period upon delivering a pace to site LV1 duringwhich all further pacing of site LV1 is inhibited, wherein the leftventricular protective period is unaffected by a pace to site LV2.

In an exemplary embodiment for implementing the LVPP, the controller isprogrammed to sense cardiac activity through right ventricular and leftventricular sensing channels, schedule delivery of paces through leftventricular pacing channels to at least two left ventricular sitesdesignated LV1 and LV2 during a cardiac cycle interval that is reset bya right ventricular sense, initiate a left ventricular protective periodfor site LV1 after a left ventricular pace to site LV1 or after a leftventricular sense during which further paces to site LV1 are inhibited,and initiate a left ventricular protective period for site LV2 after aleft ventricular pace to site LV2 or after a left ventricular senseduring which further paces to site LV1 are inhibited. The controller maybe further programmed to: 1) schedule delivery of paces through leftventricular pacing channels to one or more additional left ventricularsites and initiate a separate left ventricular protective period foreach additional site after a pace to that site or a left ventricularsense; 2) sense cardiac activity at sites LV1 and LV2 through separatesensing channels, initiate the left ventricular protective period forsite LV1 only after a left ventricular pace to site LV1 or after a leftventricular sense at site LV1, initiate the left ventricular protectiveperiod for site LV2 only after a left ventricular pace to site LV2 orafter a left ventricular sense at site LV1; 3) schedule delivery ofpaces through left ventricular pacing channels to one or more additionalleft ventricular sites and initiate a separate left ventricularprotective period for each additional site only after a pace to thatsite or a left ventricular sense at that site; and/or 4) shorten each ofthe left ventricular protective periods with increasing heart rate. Inanother embodiment, the controller is programmed to sense cardiacactivity through a right ventricular sensing channel, schedule deliveryof paces through left ventricular pacing channels to at least two leftventricular sites during a cardiac cycle interval that is reset by aright ventricular sense, and initiate a pace-initiated left ventricularprotective period after a left ventricular pace during which all but thefirst left ventricular pace delivered to a left ventricular site duringa cardiac cycle interval are inhibited. The controller may further beprogrammed to: 1) sense cardiac activity through a left ventricularsensing channel and initiate a sense-initiated left ventricularprotective period after a left ventricular sense during which all pacesto the left ventricle are inhibited; 2) define selected refractoryperiods for sensing channels such that when a sensing channel isrefractory either the sensing channel is disabled or sensed activity isignored for purposes of cardiac event detection, initiate post-pacerefractory periods for both the right and left ventricular sensingchannels when the first ventricular pace is delivered during a cardiaccycle, restart and extend the left ventricular protective period as asense-initiated left ventricular protective period if a non-refractoryleft ventricular sense occurs during a pace-initiated or sense-initiatedleft ventricular protective period, 3) after a left ventricular paceduring a pace-initiated left ventricular protective period, restart andextend the left ventricular protective period as a pace-initiated leftventricular protective period; and/or 4) shorten each of thepace-initiated and sense-initiated left ventricular protective periodswith increasing heart rate.

In an exemplary embodiment for implementing multi-site LV-only pacingwith RV safety pacing, the controller is programmed to sense cardiacactivity through right ventricular and left ventricular sensingchannels, schedule delivery of paces through left ventricular pacingchannels to at least two left ventricular sites during a cardiac cycleinterval that is reset by a right ventricular sense, wherein the leftventricular paces are delivered in time relation to expiration of anescape interval that is reset by a right ventricular sense and whereinthe expiration of the escape interval is marked by a right ventricularpseudo-pace acting as a fiducial point, initiate a left ventricularprotective period after a left ventricular sense during which one ormore left ventricular paces are inhibited, and deliver a rightventricular safety pace coincident with the right ventricularpseudo-pace if all scheduled left ventricular paces are inhibited duringa cardiac cycle interval either by a left ventricular protective periodor otherwise. The controller may further be programmed to: 1) not todeliver a right ventricular safety pace if one or more scheduled leftventricular paces are inhibited during a cardiac cycle interval eitherby a left ventricular protective period or otherwise but at least oneleft ventricular pace is scheduled outside of the left ventricularprotective period; 2) deliver no right ventricular safety pace anddeliver the left ventricular paces that were inhibited by the leftventricular protective period immediately after its expiration if one ormore scheduled left ventricular paces are inhibited during a cardiaccycle interval either by a left ventricular protective period orotherwise but at least one left ventricular pace is scheduled outside ofthe left ventricular protective period; 3) deliver a right ventricularsafety pace coincident with the right ventricular pseudo-pace andinhibit all remaining scheduled left ventricular paces during thecardiac cycle interval if all left ventricular paces scheduled to occurbefore or coincident with the right ventricular pseudo-pace areinhibited during a cardiac cycle interval either by a left ventricularprotective period or otherwise; 4) deliver a right ventricular safetypace coincident with the right ventricular pseudo-pace and deliver allremaining scheduled left ventricular paces that fall outside of a leftventricular protective period and are not otherwise inhibited during thecardiac cycle interval at their scheduled times if all left ventricularpaces scheduled to occur before or coincident with the right ventricularpseudo-pace are inhibited during a cardiac cycle interval either by aleft ventricular protective period or otherwise; 5) deliver a rightventricular safety pace coincident with the right ventricularpseudo-pace and deliver all remaining scheduled left ventricular pacesthat fall outside of the left ventricular protective period immediatelyafter its expiration if all left ventricular paces scheduled to occurbefore or coincident with the right ventricular pseudo-pace areinhibited during a cardiac cycle interval either by a left ventricularprotective period or otherwise; 6) deliver no right ventricular safetypace if all left ventricular paces scheduled to occur before orcoincident with the right ventricular pseudo-pace are not inhibitedduring a cardiac cycle interval either by a left ventricular protectiveperiod or otherwise; 7) enforce a minimum cardiac cycle interval andinhibit left ventricular paces that would otherwise violate thespecified minimum cardiac cycle interval; 8) inhibit left ventricularpaces that would otherwise violate a specified minimum cardiac cycleinterval and deliver the left ventricular paces that were inhibitedimmediately after the minimum cardiac cycle interval has lapsed; and/or9) enforce a minimum cardiac cycle interval by inhibiting leftventricular paces that would otherwise violate the specified minimumcardiac cycle interval and further programmed to deliver one or moreleft ventricular paces to specified sites and at specified times afterthe minimum cardiac cycle interval has lapsed, if all left ventricularpaces during a cardiac cycle interval are inhibited for violating thespecified minimum cardiac cycle interval.

In an exemplary embodiment for implementing biventricular-triggeredpacing in a multi-site LV pacing context, the controller is programmedto: sense cardiac activity through a right ventricular sensing channel;operate in a normal pacing mode or a biventricular-triggered pacingmode; in a normal pacing mode, schedule delivery of paces through leftventricular pacing charnels to at least two left ventricular sitesduring a cardiac cycle interval that is reset by a right ventricularsense; and in a biventricular-triggered pacing mode, when triggered by aright ventricular sense, deliver a pace to the right ventricle through aright ventricular pacing channel and deliver a single pace to the leftventricle at a selected left ventricular site. The controller mayfurther be programmed: 1) such that the selected left ventricular sitepaced in the biventricular-triggered pacing mode is selected from amongthe left ventricular sites paced in the normal mode, and/or 2) such thatthe selected left ventricular site paced in the biventricular-triggeredpacing mode is different from the left ventricular sites paced in thenormal mode. In another embodiment, the controller is programmed to:sense cardiac activity through a right ventricular sensing channel;operate in a normal pacing mode or a biventricular-triggered pacingmode; in a normal pacing mode, schedule delivery of paces through leftventricular pacing channels to at least two left ventricular sitesduring a cardiac cycle interval that is reset by a right ventricularsense; and in a biventricular-triggered pacing mode, when triggered by aright ventricular sense, deliver a pace to the right ventricle through aright ventricular pacing channel and deliver multiple paces to the leftventricle at selected left ventricular sites. The controller may furtherbe programmed: 1) such that the selected left ventricular sites paced inthe biventricular-triggered pacing mode are selected from among the leftventricular sites paced in the normal mode; 2) such that at least one ofthe selected left ventricular sites paced in the biventricular-triggeredpacing mode is different from the left ventricular sites paced in thenormal mode; 3) in the biventricular-triggered mode, to deliver at leastone first left ventricular pace coincident with the right ventricularpace immediately after a right ventricular sense and then deliver atleast one subsequent left ventricular pace after a selected interval; 4)such that the subsequent left ventricular paces are delivered atselected intervals after the first left ventricular pace that are thesame as the intervals between left ventricular paces used in the normalmode; and/or 5) such that the subsequent left ventricular paces aredelivered at selected intervals after the first left ventricular pacethat are the different from the intervals between left ventricular pacesused in the normal mode.

The invention has been described in conjunction with the foregoingspecific embodiments. It should be appreciated that those embodimentsmay also be combined in any manner considered to be advantageous. Also,many alternatives, variations, and modifications will be apparent tothose of ordinary skill in the art. Other such alternatives, variations,and modifications are intended to fall within the scope of the followingappended claims.

What is claimed is:
 1. A cardiac pacing device, comprising: pulsegeneration circuitry for generating pacing pulses; sensing circuitry forsensing cardiac electrical activity; a controller for detecting cardiacevents that define pacing timing intervals and for controlling thedelivery of pacing pulses in accordance with a programmed mode; a switchmatrix operable by the controller for connecting the pulse generationcircuitry and sensing circuitry to selected electrodes in order to formselected sensing and pacing channels; wherein the controller isprogrammed to: sense cardiac activity through right ventricular and leftventricular sensing channels; schedule delivery of paces through leftventricular pacing channels to at least two left ventricular sitesduring a cardiac cycle interval that is reset by a right ventricularsense, wherein each of the left ventricular paces is delivered at anindividually specified pacing instant in relation to expiration of anescape interval that is reset by a right ventricular sense; initiate aleft ventricular protective period after a left ventricular sense;determine whether or not the pacing instants of all of a plurality ofscheduled left ventricular paces fall within the initiated leftventricular protective period during a cardiac cycle and, if so, delivera right ventricular pace upon expiration of the escape interval.
 2. Thedevice of claim 1 wherein the controller is further programmed suchthat, if one or more scheduled left ventricular paces are inhibitedduring a cardiac cycle interval by a left ventricular protective periodbut at least one left ventricular pace is scheduled outside of the leftventricular protective period, no right ventricular safety pace isdelivered.
 3. The device of claim 1 wherein the controller is furtherprogrammed to, if one or more scheduled left ventricular paces areinhibited during a cardiac cycle interval by a left ventricularprotective period but at least one left ventricular pace is scheduledoutside of the left ventricular protective period, deliver no rightventricular safety pace and deliver the left ventricular paces that wereinhibited by the left ventricular protective period immediately afterits expiration.
 4. The device of claim 1 wherein the controller isfurther programmed to, if all left ventricular paces scheduled to occurbefore or coincident with expiration of the escape interval areinhibited during a cardiac cycle interval by a left ventricularprotective period, deliver a right ventricular safety pace coincidentwith expiration of the escape interval and inhibit all remainingscheduled left ventricular paces during the cardiac cycle interval. 5.The device of claim 1 wherein the controller is further programmed to,if all left ventricular paces scheduled to occur before or coincidentwith expiration of the escape interval are inhibited during a cardiaccycle interval by a left ventricular protective period, deliver a rightventricular safety pace coincident with expiration of the escapeinterval and deliver all remaining scheduled left ventricular paces thatfall outside of a left ventricular protective period and are nototherwise inhibited during the cardiac cycle interval at their scheduledtimes.
 6. The device of claim 1 wherein the controller is furtherprogrammed to, if all left ventricular paces scheduled to occur beforeor coincident with expiration of the escape interval are inhibitedduring a cardiac cycle interval by a left ventricular protective period,deliver a right ventricular safety pace coincident with expiration ofthe escape interval and deliver all remaining scheduled left ventricularpaces that fall outside of the left ventricular protective periodimmediately after its expiration.
 7. The device of claim 1 wherein thecontroller is further programmed to, if all left ventricular pacesscheduled to occur before or coincident with expiration of the escapeinterval are not inhibited during a cardiac cycle interval by a leftventricular protective period, deliver no right ventricular safety pace.8. The device of claim 1 wherein the controller is programmed to enforcea minimum cardiac cycle interval and inhibit left ventricular paces thatwould otherwise violate the specified minimum cardiac cycle interval. 9.The device of claim 1 wherein the controller is programmed to inhibitleft ventricular paces that would otherwise violate a specified minimumcardiac cycle interval and deliver the left ventricular paces that wereinhibited immediately after the minimum cardiac cycle interval haslapsed.
 10. The device of claim 1 wherein the controller is programmedto enforce a minimum cardiac cycle interval by inhibiting leftventricular paces that would otherwise violate the specified minimumcardiac cycle interval and further programmed to, if all leftventricular paces during a cardiac cycle interval are inhibited forviolating the specified minimum cardiac cycle interval, deliver one ormore left ventricular paces to specified sites and at specified timesafter the minimum cardiac cycle interval has lapsed.
 11. A method foroperating a cardiac pacing device, comprising: sensing cardiac activitythrough right ventricular and left ventricular sensing channels;scheduling delivery of paces through left ventricular pacing channels toat least two left ventricular sites during a cardiac cycle interval thatis reset by a right ventricular sense, wherein each of the leftventricular paces is delivered at an individually specified pacinginstant in relation to expiration of an escape interval that is reset bya right ventricular sense; initiating a left ventricular protectiveperiod after a left ventricular sense; determining whether or not thepacing instants of all of a plurality of scheduled left ventricularpaces fall within the initiated left ventricular protective period and,if so, delivering a right ventricular pace upon expiration of the escapeinterval.
 12. The method of claim 11 wherein, if one or more scheduledleft ventricular paces are inhibited during a cardiac cycle interval bya left ventricular protective period but at least one left ventricularpace is scheduled outside of the left ventricular protective period, noright ventricular safety pace is delivered.
 13. The method of claim 11further comprising, if one or more scheduled left ventricular paces areinhibited during a cardiac cycle interval by a left ventricularprotective period but at least one left ventricular pace is scheduledoutside of the left ventricular protective period, delivering no rightventricular safety pace and delivering the left ventricular paces thatwere inhibited by the left ventricular protective period immediatelyafter its expiration.
 14. The method of claim 11 further comprising, ifall left ventricular paces scheduled to occur before or coincident withexpiration of the escape interval are inhibited during a cardiac cycleinterval by a left ventricular protective period, delivering a rightventricular safety pace coincident with expiration of the escapeinterval and inhibiting all remaining scheduled left ventricular pacesduring the cardiac cycle interval.
 15. The method of claim 11 furthercomprising, if all left ventricular paces scheduled to occur before orcoincident with expiration of the escape interval are inhibited during acardiac cycle interval by a left ventricular protective period,delivering a right ventricular safety pace coincident with expiration ofthe escape interval and delivering all remaining scheduled leftventricular paces that fall outside of a left ventricular protectiveperiod and are not otherwise inhibited during the cardiac cycle intervalat their scheduled times.
 16. The method of claim 11 further comprising,if all left ventricular paces scheduled to occur before or coincidentwith expiration of the escape interval are inhibited during a cardiaccycle interval by a left ventricular protective period, delivering aright ventricular safety pace coincident with expiration of the escapeinterval and delivering all remaining scheduled left ventricular pacesthat fall outside of the left ventricular protective period immediatelyafter its expiration.
 17. The method of claim 11 further comprising, ifall left ventricular paces scheduled to occur before or coincident withexpiration of the escape interval are not inhibited during a cardiaccycle interval by a left ventricular protective period, delivering noright ventricular safety pace.
 18. The method of claim 11 furthercomprising enforcing a minimum cardiac cycle interval and inhibitingleft ventricular paces that would otherwise violate the specifiedminimum cardiac cycle interval.
 19. The method of claim 11 furthercomprising inhibiting left ventricular paces that would otherwiseviolate a specified minimum cardiac cycle interval and delivering theleft ventricular paces that were inhibited immediately after the minimumcardiac cycle interval has lapsed.
 20. The method of claim 11 furthercomprising enforcing a minimum cardiac cycle interval by inhibiting leftventricular paces that would otherwise violate the specified minimumcardiac cycle interval and, if all left ventricular paces during acardiac cycle interval are inhibited for violating the specified minimumcardiac cycle interval, delivering one or more left ventricular paces tospecified sites and at specified times after the minimum cardiac cycleinterval has lapsed.